Functional activation studies in health and disease often depend upon perfusion related signals to localize the source of brain activity. The goal of this proposal is to investigate perfusion related signals measured using Optical Intrinsic Signals (OIS), Near Infrared Spectroscopy (NIRS), functional Magnetic Resonance Imaging (fMRI) and Electroencephalography (EEG) during a variety of stimulus conditions. The application of different neuroimaging techniques in both animals and humans will provide a comprehensive view of the timing, distribution and capacities of these perfusion related signals and how perfusion related signals from different modalities relate. We will perform functional activation studies using OIS (multispectral and single wavelength), NIRS, fMRI, fluorescent dyes and electrical measures, to determine the relationship in space and time between these perfusion dependent, and evoked potential maps. The proposed experiments will provide a better understanding of the cascade of events collectively called the hemodynamic response. We will do this in different sensory systems of rodents and humans using a variety of stimulus and behavioral paradigms. In humans, perfusion related signals obtained using OIS and electrophysiologic methods intraoperatively will be compared with NIRS and fMRI in the same subjects. In both species, maps and the temporal profile of responses obtained from each modality will be compared within and across subjects following image registration. The proposed studies will begin with investigating the role of nitric oxide (NO) in mediating perfusion related responses. We will also characterize the nature of functional hemoglobin changes following functional activation using optical spectroscopy. Having characterized the normal characteristics of functional perfusion related responses, we will then determine how perfusion related signals are affected by various challenges (including seizure, cortical spreading depression, development, and experience- dependent plasticity). Finally, we will investigate and compare the relationship between perfusion related signals across multiple modalities. This proposal is a natural extension to our active grant where the focus was to characterize the basic temporal and spatial characteristics of optical signal responses to peripheral somesthetic stimulation. Since the coupling of brain function to cerebral perfusion provides the basis for a number of functional neuroimaging techniques, a precise knowledge of the specific underlying physiological mechanisms and their characteristics is essential. The experiments described here will help us achieve that goal.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH052083-09
Application #
6797230
Study Section
Special Emphasis Panel (ZRG1-BDCN-6 (01))
Program Officer
Glanzman, Dennis L
Project Start
1995-09-30
Project End
2007-02-28
Budget Start
2004-05-01
Budget End
2005-02-28
Support Year
9
Fiscal Year
2004
Total Cost
$343,125
Indirect Cost
Name
University of California Los Angeles
Department
Neurology
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
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Chang, Joshua C; Shook, Lydia L; Biag, Jonathan et al. (2010) Biphasic direct current shift, haemoglobin desaturation and neurovascular uncoupling in cortical spreading depression. Brain 133:996-1012
Sheth, Sameer A; Prakash, Neal; Guiou, Michael et al. (2009) Validation and visualization of two-dimensional optical spectroscopic imaging of cerebral hemodynamics. Neuroimage 47 Suppl 2:T36-43
Prakash, Neal; Uhlemann, Falk; Sheth, Sameer A et al. (2009) Current trends in intraoperative optical imaging for functional brain mapping and delineation of lesions of language cortex. Neuroimage 47 Suppl 2:T116-26
Prakash, Neal; Biag, Jonathan D; Sheth, Sameer A et al. (2007) Temporal profiles and 2-dimensional oxy-, deoxy-, and total-hemoglobin somatosensory maps in rat versus mouse cortex. Neuroimage 37 Suppl 1:S27-36
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Guiou, Michael; Sheth, Sameer; Nemoto, Masahito et al. (2005) Cortical spreading depression produces long-term disruption of activity-related changes in cerebral blood volume and neurovascular coupling. J Biomed Opt 10:11004
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Sheth, Sameer A; Nemoto, Masahito; Guiou, Michael et al. (2004) Linear and nonlinear relationships between neuronal activity, oxygen metabolism, and hemodynamic responses. Neuron 42:347-55

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